Article Figures & Data
Figures
- Figure 1.
Invading epithelial tumor cells and the associated tumor microenvironment. Dissolution of the basement membrane is accompanied by the production and secretion of numerous ECM components, including the collagens, fibronectin, laminin, and HA, as part of the myofibroblast-mediated desmoplastic reaction. Infiltrating immune cells also contribute to the signaling involved in the desmoplastic reaction. Expansion of the stromal compartment and production of the ECM proteins are thought to result in greater intratumoral pressure and contribute to a reduction in effective drug delivery. Inset, chemical structure of HA. HA is a linear polysaccharide composed of repeating units of glucuronic acid and N-acetylglucosamine. HA is a nonsulfated GAG and participates as an integral component of the ECM.
Tables
ECM component Functional role in chemoresistance Collagen I, III, IV Enhances tumor cell proliferation, structural support of ECM Decorin Binds TGF-β, tightens collagen fibrils HA Synergizes with collagen network, increases interstitial fluid pressure Versican Enhances tumor cell proliferation, confers resistance to apoptosis Fibronectin Confers resistance to apoptosis Laminin Confers resistance to apoptosis Osteonectin/SPARC Enhances tumor cell proliferation and metastasis - Table 1.
Early clinical studies investigating the coadministration of bovine hyaluronidase with chemotherapy
Study Trial type Tumor type Chemotherapy Number of patients Endpoint Results Klocker et al. (16) Phase II Adv. SCC-HN Cisplatin/vindesine 48 Response CR in 84%, 47% survival >5 y Baumgartner et al. (12) Phase III Bladder cancer Mitomycin C 56 Recurrence 27% vs. 59% recurrence in HYAL-treated vs. untreated Pillwein et al. (14) Phase II Malignant brain Carboplatin/etoposide 40 Survival 3-y survival, 84% vs. 50% in HYAL-treated vs. untreated Smith et al. (13) Phase I Kaposi's sarcoma Vinblastine 6 Toxicity/recurrence 0% vs. 50% recurrence in HYAL-treated lesions, no added toxicity Baumgartner et al. (20) Phase I Gastrointestinal and others Adriamycin and others 12 Toxicity/recurrence PR/MR in 5 of 12 resistant, no added toxicity Abbreviations: Adv. SCC-HN, advanced squamous cell carcinoma of the head and neck; CR, complete response; HYAL, hyaluronidase; MR, minimal response; PR, partial response
Volume 1, Issue 4
